EXPOSURE TO ACUTE STRESS INDUCES BRAIN INTERLEUKIN-1-BETA PROTEIN IN THE RAT

Peripheral immune stimulation such as that provided by lipopolysacchar ide (LPS) has been reported to increase brain levels of IL-1 beta mRNA , immunoreactivity, and bioactivity. Stressors produce many of the sam e neural and endocrine responses as those that follow LPS, but the imp act of stressors on brain interleukin-1 beta (IL-1 beta) has not been systematically explored. An ELISA designed to detect IL-1 beta was use d to measure levels of IL-1 beta protein in rat brain. Brain IL-1 beta was explored after exposure to inescapable shock (IS; 100 1.6 mA tail shocks for 5 sec each) and LPS (1 mg/kg) as a positive control. Rats were killed either immediately or 2, 7, 24, or 48 hr after IS. Brains were dissected into hypothalamus, hippocampus, cerebellum, posterior c ortex, and nucleus tractus solitarius regions. LPS produced widespread increases in brain IL-1 beta, but IS did not. Adrenal glucocorticoids are known to suppress IL-1 beta production in both the periphery and brain. Thus, it was possible that the stressor did provide stimulus in put to the brain IL-1 beta system(s), but that the production of IL-1 beta protein was suppressed by the rapid and prolonged high levels of glucocorticoids produced by IS. To test this possibility rats were adr enalectomized or given sham surgery, with half of the adrenalectomized rats receiving corticosterone replacement to maintain basal corticost erone levels. IS produced large increases in brain IL-1 beta protein i n the adrenalectomized subjects 2 hr after stress, whether basal corti costerone levels had been maintained. Thus elimination of the stress-i nduced rise in corticosterone unmasked a robust and widespread increas e in brain IL-1 beta.